Palmitoylation of BMPR1a regulates neural stem cell fate
| Autor: | Iliana Mebert, Dominik Kollegger, Pawel Pelczar, Thomas Wegleiter, Adriano Molteni, Daniel Gonzalez-Bohorquez, Kilian Buthey, Sebastian Jessberger, Martina Hruzova, Muhammad Khadeesh bin Imtiaz, Andrin Abegg |
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| Přispěvatelé: | University of Zurich, Wegleiter, Thomas |
| Rok vydání: | 2019 |
| Předmět: |
Lipoylation
Neurogenesis 610 Medicine & health Context (language use) Biology Bone morphogenetic protein Mice neural stem cell 03 medical and health sciences 0302 clinical medicine Neural Stem Cells oligodendrogenesis Palmitoylation Animals BMP receptor palmitoylation Bone Morphogenetic Protein Receptors Type I Cells Cultured reproductive and urinary physiology 030304 developmental biology 1000 Multidisciplinary 0303 health sciences Multidisciplinary 10242 Brain Research Institute Biological Sciences Embryonic stem cell Neural stem cell BMPR1A nervous system diseases Cell biology nervous system 570 Life sciences biology lipids (amino acids peptides and proteins) biological phenomena cell phenomena and immunity Lipid modification 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America PNAS |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1912671116 |
| Popis: | Significance Neural stem cells (NSCs) generate neurons and glia throughout life. Using global S-acylation profiling in NSCs, we identified BMPR1a, a main driver of embryonic and postnatal development to be S-acylated. We showed that BMPR1a is S-acylated in embryonic stem cells and NSCs, and identified 3 distinct S-acylated sites. We showed that S-acylation of BMPR1a is important for BMPR1a trafficking in vitro and characterized the importance of BMPR1a S-acylation for canonical and noncanonical BMP signaling. We generated a knock-in mouse for BMPR1a, deficient for S-acylation at site 180, and identified BMPR1a S-acylation as a regulatory mechanism controlling oligodendrogenesis in vitro and in vivo. Thus, we here provide insight on how the diverse output of BMPR1a-dependent signaling is regulated throughout development. Neural stem cells (NSCs) generate neurons and glial cells throughout embryonic and postnatal brain development. The role of S-palmitoylation (also referred to as S-acylation), a reversible posttranslational lipid modification of proteins, in regulating the fate and activity of NSCs remains largely unknown. We used an unbiased screening approach to identify proteins that are S-acylated in mouse NSCs and showed that bone morphogenic protein receptor 1a (BMPR1a), a core mediator of BMP signaling, is palmitoylated. Genetic manipulation of S-acylated sites affects the localization and trafficking of BMPR1a and leads to altered BMP signaling. Strikingly, defective palmitoylation of BMPR1a modulates NSC function within the mouse brain, resulting in enhanced oligodendrogenesis. Thus, we identified a mechanism regulating the behavior of NSCs and provided the framework to characterize dynamic posttranslational lipid modifications of proteins in the context of NSC biology. |
| Databáze: | OpenAIRE |
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